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VEGF/VEGFR2 signaling regulates hippocampal axon branching during development

Axon branching is crucial for proper formation of neuronal networks. Although originally identified as an angiogenic factor, VEGF also signals directly to neurons to regulate their development and function. Here we show that VEGF and its receptor VEGFR2 (also known as KDR or FLK1) are expressed in m...

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Main Authors: Luck, Robert (Author) , Urban, Severino (Author) , Karakatsani, Andromachi (Author) , Harde, Eva (Author) , Sambandan, Sivakumar (Author) , Nicholson, LaShae (Author) , Haverkamp, Silke (Author) , Mann, Rebecca (Author) , Martín-Villalba, Ana (Author) , Schuman, Erin (Author) , Acker-Palmer, Amparo (Author) , Ruiz de Almodóvar, Carmen (Author)
Format: Article (Journal)
Language:English
Published: Dec 23, 2019
In: eLife
Year: 2019, Volume: 8, Pages: e49818
ISSN:2050-084X
DOI:10.7554/eLife.49818
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7554/eLife.49818
Verlag, lizenzpflichtig, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927742
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Author Notes:Robert Luck, Severino Urban, Andromachi Karakatsani, Eva Harde, Sivakumar Sambandan, LaShae Nicholson, Silke Haverkamp, Rebecca Mann, Ana Martin-Villalba, Erin Margaret Schuman, Amparo Acker-Palmer, Carmen Ruiz de Almodóvar
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Summary:Axon branching is crucial for proper formation of neuronal networks. Although originally identified as an angiogenic factor, VEGF also signals directly to neurons to regulate their development and function. Here we show that VEGF and its receptor VEGFR2 (also known as KDR or FLK1) are expressed in mouse hippocampal neurons during development, with VEGFR2 locally expressed in the CA3 region. Activation of VEGF/VEGFR2 signaling in isolated hippocampal neurons results in increased axon branching. Remarkably, inactivation of VEGFR2 also results in increased axon branching in vitro and in vivo. The increased CA3 axon branching is not productive as these axons are less mature and form less functional synapses with CA1 neurons. Mechanistically, while VEGF promotes the growth of formed branches without affecting filopodia formation, loss of VEGFR2 increases the number of filopodia and enhances the growth rate of new branches. Thus, a controlled VEGF/VEGFR2 signaling is required for proper CA3 hippocampal axon branching during mouse hippocampus development.
Item Description:Gesehen am 21.04.2020
Physical Description:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.49818

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